The number of immunocompromised patients is increasing due to the intensive therapy being administered those with cancer, organ transplant, and HIV infection. Fungal infections are one of the important opportunistic infections in immunocompromised patients. Early diagnosis is difficult, and the prognosis of these patinas is usually poor. Several methods of diagnosis for fungal infections have been developed: detection of antigens of the infected fungi from the sera is useful for early diagnosis; polymerise chain reaction (PCR) technology may be the most valuable method for the diagnosis of fungal infection in immunocompromised patients, and antifungal agents are the drugs used to the fungal infections in those patients. However, there are only five drugs available to fungal infections in Japan. Although amphotericin B is the recommended first choice for treatment of invasive aspergillosis, its use for immunocompromised patients is limited because of its adverse effects. Novel antifungal agents (azoles, amphotericin B drug deliver system, and 1, 3-β-D-glucan sythetase inhibitors) have been developed and some of these compounds undergoing clinical trials.

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Recent advances in the research on host defense mechanisms against infections with Candida and Aspergillus were reviewed. Modes of the defense mechanisms were divided into three phases by the different physiological circumstances surrounding the fungi: 1, the exocrine fluid in which fungi exist on the mucosal membranes; 2, the tissues invaded by fungi with the circulating blood; and 3, the limited lesions where fungi continue to be alive with a restricted blood flow. In each defense mechanism, the roles of the endogenous antifungal substances such as lactoferrin, defensins and calprotectin and leukocytes were discussed.

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We report a case of fixed sporotrichosis in a 2-year-old girl who showed a reddish nodule on her left cheek for 1 year without trauma. Fungiflora-Y staining showed fungal elements from the exudate on the erosion of this nodule. Sporothrix schenckii was isolated from a culture of the fungus taken from the biopsy specimen. Treatment with itraconazole 4.5mg/kg/day for 16 weeks resulted in an atrophic scar after 2.1mg/kg/day for 8 weeks without side effects. Six months later, her eruption recurred and was treated with potassium iodide for 21 weeks with complete resolution. During the 1 year follow up period, there was no recurrence. Six cases of sporotrichosis in children including ours have been reported in Japan. Each case showed complete resolution and no recurrence. However, careful follow-up is believed to be necessary based on our case.

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Phaeoacremonium parasiticum was identified as the causative agent of a phaeomycotic cyst seen just below the right knee of a 59-year-old healthy woman. She had no history of trauma. Direct KOH examination of the pus aspirated from the subcutaneous nodule revealed abundant mycelia, which were not too deeply brown in color. The nodule was surgically excised, and there was no recurrence during a half year of observation. Tissue section of the excised material revealed rather a large cavity extending from the cutis to the subcutis. The cavity had a thick wall composed of granulomatous tissues. Mycelial and yeast-like fungal elements were seen within the cavity and the granulomatous tissues. A dematiaceous fungus was cultured from both pus and the excised material. The isolates were characterized by a dark green to black colony, unbranched or infrequently branched, brownish conidiophores bearing an aculeate monophialide with a narrow funnel-shaped collarette, and slimy, hyaline, one-celled, ellipsoid to allantoid conidia.

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The anti-inflammatory effect of lanoconazole (LCZ) was investigated in vivo and in vitro. The effect of LCZ was evaluated on the inflammatory reactions elicited by intradermal injection of ovalbumin to ovalbumin-immunized rabbits, as an Arthus phenomenon. A one or two % cream preparation of LCZ was topically applied on the lesion daily after challenging injection until the inflamation had diminished. By macroscopic observation and measuring the diameter of edema, erythema, hemorrhage and necrosis, the effects of LCZ on the reactions were compared with the reactions of the sites administered with cream vehicle as reference agent. Two % LCZ showed an anti-hemorrhagic effect. The in vitro effect of LCZ on production and functions of an inflammatory cytokine, TNF was also examined. LCZ suppressed the production of TNF by murine peritoneal macrophages at 20μg/ml and the adhesion of neutrophils at 100μg/ml. Moreover, LCZ significantly suppressed the growth inhibitory activity of TNF against L929 fibroblasts at 0.5μg/ml. A very low concentration of LCZ might protect the fibroblasts from immunological cytotoxicity in vivo. These findings suggest that LCZ has a suppressive activity to inflammatory responses and this suppressive action may be due to its protective activity to cells like fibroblasts.

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Disseminated aspergillosis is an uncommon and unpredictable complication in severely immunocompromised patients and poses a challenging problem in the management and care of seriously ill patients receiving intensive care therapy. We report an autopsied case of disseminated aspergillosis occurring in a 31-year-old female patient who was treated for HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome. She initially presented with edema and proteinuria at a pregnancy check-up. At gestational age 33 weeks and 2 days, she had right lower abdominal pain, nausea, and jaundice. The next day she delivered a male neonate transvaginally, followed by excessive postpartum uterine bleeding. Although an emergency hysterectomy was performed, her hemorrhagic diathesis could not be controlled even after transcatheter embolization of the internal iliac arteries with subsequent ligation and repeated blood transfusions totalling to 31, 070ml. She eventually died of a cerebral hemorrhage 21 days after the parturition. Autopsy showed generalized jaundice and petechiae, as well as extensive hemorrhage observed in the abdominal wall, peritoneal cavity, and retroperitoneal and pelvic spaces. In addition, there were multifocal hemorrhages found in the left temporal, right frontal and posterior lobes of the cerebrum, and pons. Disseminated aspergillosis was found in the lungs, trachea, brain, esophagus, stomach, heart, and thyroid gland. These findings suggest that systemic postoperative complications, associated with massive blood transfusions and hepatic failure, mutually contribute to the overall deterioration of host defense mechanism, and may underlie the occurrence of devastating systemic fungal infection.

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Sporothrix schenckii is a well-known pathogenic dimorphic fungus. In this study, we focused on the plasma membrane ultrastructures of giant cells of S. schenckii seen mainly on Sabouraud's dextrose agar slant medium. In the organisms grown for 1, 2, 3, 4, 6 and 8 weeks at 27 and 37°C on brain heart infusion and Sabouraud's dextrose agar slant media, the number of conidia, hyphae, brownish and non-brownish giant cells were counted in ten separated areas under light microscope (×100) to determine the culture conditions under which giant cells were generated. The results showed that brownish giant cells were predominantly seen after longer cultivation periods. Using freeze-fracture electron microscopy, larger oval- or round shaped cells can be identified as conidia by their plasma membrane ultrastructure characteristics, i. e, trench-like invaginations seen in ordinary mature conidia (Maeda M et al.; Can J Microbiol 33: 40, 1987). From these structural features seen by freeze-fracture electron microscopy, giant cells appeared possibly be conidia and were suggested to be starved because of their predominant existence under longer cultivation conditions.

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The protective effects of a “hozai” type of Kampo medicine, Juzen-taiho-to (Shi-quan-da-bu-tang, TJ-48), Hochu-ekki-to (Bu-zhong-yi-qi-tang, TJ-41) or Ninjin-yoei-to (Ren-shen-yang-rong-tang, TJ-108) on experimental candidiasis in immunosuppressed mice were investigated. ICR mice, which were immunosuppressed by injection of cyclophosphamide or prednisolone, were given these medicines orally and challenged intravenously with Candida albicans (day 0). Treatments with a daily dose of 1g/kg/day of TJ-48 or that of 1 or 2g/kg/day of TJ-108 for 4 consecutive days from day-4 significantly prolonged the survival time of the Candida-infected mice pretreated with cyclophosphamide. Treatments with a daily dose of 1g/kg/day of TJ-48 for 4 consecutive days from day 0, but not from day-4, significantly prolonged the life span of the Candida-infected mice pretreated with prednisolone. On the basis of these results and previous findings, characteristics of these kampo medicines as therapeutic agents against candidiasis in immunosuppressed hosts were discussed.

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A fifty five-year old woman suffered from itching and scaling of the edge of her eyelid. She had long used topical corticosteroid for this condition. Direct examination of the scale by Parker KOH showed numerous fungal elements of spores and hyphae of Malassezia furfur. She was treated with oral itraconazole (100mg daily or twice a week) for 8 weeks and was cured clinically and mycologically. The result suggests the possibility of treatment with an anti-fungal drug for seborrhoeic blepharitis or seborrhoeic dermatitis.

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